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Therapeutic Class Overview Calcium Channel Blockers

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Therapeutic Class Overview Calcium Channel Blockers INTRODUCTION • Approximately 121.5 million American adults are living with some form of cardiovascular disease (consisting of coronary heart disease, heart failure, stroke, and hypertension) according to the American Heart Association Heart (AHA) Disease and Stroke Statistics 2019 update. Cardiovascular disease accounts for nearly 840,678 deaths in the United States (US) annually (Benjamin et al 2019). • Calcium channel blockade has certain effects that are specific to cardiac function. Coronary vascular smooth muscle relaxes when calcium channels are blocked which increases the flow of oxygenated blood into the myocardium and lowers coronary vascular resistance. In addition, calcium channel blocking agents (also called calcium channel blockers) decrease peripheral vascular resistance by relaxing arteriolar smooth muscle. Both coronary and systemic vasodilation serve to reduce cardiac workload (Kannam et al 2019, Dobesh PP 2017, Michel T 2011). • The movement of calcium ions is essential for the function of all types of muscle, including cardiac muscle and vascular smooth muscle. For both cardiac and smooth muscle, the flow of calcium ions into the muscle cells through specific channels allows muscle contraction to occur. When this flow is reduced, the result is a weakening of muscle contraction and relaxation of muscle tissue (Micromedex 2.0 2019, Kannam et al 2019). • The calcium channel blocking agents include dihydropyridines, which are similar in chemical structure, and non- dihydropyridines, which are a structurally heterogeneous group. Although they have different binding sites on the L-type calcium channel, both block the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. The non-dihydropyridines also block the T-type calcium channel in the atrioventricular (AV) node (Micromedex 2.0 2019, Kannam et al 2019, Dobesh PP 2017, Michel T 2011, Saseen 2017). • Dihydropyridines are more potent vasodilators than non-dihydropyridines due to greater selectivity for vascular smooth muscle. They have little effect on cardiac muscle contractility or conduction (Micromedex 2.0 2019, Kannam et al 2019). All available dihydropyridine calcium channel blocking agents can be used in the treatment of hypertension, with the exception of nimodipine and immediate release nifedipine capsules. Although not a first-line treatment in all ○ hypertensive patients, the dihydropyridines are generally effective but differ somewhat in other properties and effects. Amlodipine, oral nicardipine, and long-acting nifedipine are effective treatment options for chronic stable angina. Short-acting agents, such as short-acting nifedipine, should be avoided due to increased cardiovascular and mortality ○ risks in some patients as well as significant adverse effects, such as reflex tachycardia. Amlodipine is also indicated to reduce the risk of hospitalization due to angina and to reduce the risk of a coronary revascularization procedure in patients with recently documented coronary artery disease (CAD). Amlodipine is the only calcium channel blocker that is Food and Drug Administration (FDA)-approved in combination with a nonsteroidal anti-inflammatory drug (NSAID). Consensi (amlodipine/celecoxib) was FDA-approved on May 31, ○ 2018 for the treatment of hypertension and osteoarthritis. • The non-dihydropyridine calcium channel blocking agents include diltiazem and verapamil and both agents are available in a variety of modified-release delivery systems that alter their pharmacokinetic properties, including onset and duration of action (Micromedex 2.0 2019). Non-dihydropyridines dilate the arteries somewhat less than dihydropyridines, but they also reduce heart rate and contractility (Micromedex 2.0 2019, Kannam et al 2019, Weber et al 2014). The non-dihydropyridine calcium channel blocking agents are indicated for use in the treatment of angina, arrhythmias, and hypertension. Diltiazem is a potent coronary vasodilator but is only a mild arterial vasodilator. ○ Although it decreases AV node conduction, diltiazem does not have negative inotropic properties. Verapamil dilates coronary and peripheral arteries. It also slows conduction through the AV node and has negative inotropic and chronotropic effects (Micromedex 2.0, 2019). Guidelines stipulate that a non-dihydropyridine calcium channel blocker may be prescribed in certain patients, often with co-morbid indications. Non-dihydropyridine calcium-channel blocking agents are not recommended for the ○ routine treatment of heart failure because of their negative inotropic action and risk of worsening heart failure (Yancy et al 2013, Yancy et al 2016, Yancy et al 2017). Caution is also advised in elderly patients. Guidelines generally reserve non-dihydropyridine calcium channel blockers for patients with high risk cardiovascular diseases and Data as of November 15, 2019 AG-U/KS-U/DKB Page 1 of 18 This information is considered confidential and proprietary to OptumRx. It is intended for internal use only and should be disseminated only to authorized recipients. The contents of the therapeutic class overviews on this website ("Content") are for informational purposes only. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Patients should always seek the advice of a physician or other qualified health provider with any questions regarding a medical condition. Clinicians should refer to the full prescribing information and published resources when making medical decisions. arrhythmias; therefore, they are usually reserved for progressive cardiovascular and heart disease (Al-Khatib et al 2017, American Geriatrics Society 2015, Amsterdam et al 2014, Fihn et al 2014, Go et al 2014, January et al 2014, KDIGO 2012, Williams et al 2018, Montalescot et al 2013, Page et al 2016, Rosendorff et al 2015, Weber et al 2014). • Calcium channel blockers are also included in various combination products (eg, amlodipine-benazepril); however, these combination agents are not included in this review. • Since there are several branded agents that contain the same generic component, the remaining tables in the review are organized by generic name. This review encompasses all dosage forms and strengths with the exception of injectable indications and formulations used primarily in an institutional setting. • Medispan Therapeutic Class: Calcium Channel Blockers Table 1. Medications Included Within Class Review Drug Generic Availability Dihydropyridines Adalat CC (nifedipine extended-release) Consensi (amlodipine/celecoxib) - Felodipine extended-release Isradipine Katerzia (amlodipine suspension) - Nicardipine Nimodipine Nisoldipine extended-release Norvasc (amlodipine) Nymalize (nimodipine) - Procardia (nifedipine) Procardia XL (nifedipine extended-release) Sular (nisoldipine extended-release) Non- dihydropyridines Calan (verapamil) tablet Calan SR (verapamil extended-release) tablet Cardizem (diltiazem) tablet Cardizem CD* (diltiazem extended-release) capsule † Cardizem LA (diltiazem extended-release) tablet ‡ Dilacor XR (diltiazem extended-release) capsule § Tiazac (diltiazem extended-release) capsule Verelan (verapamil sustained-release) capsule Verelan PM (verapamil extended-release) capsule *Cartia XT is a branded generic of Cardizem CD. †Matzim LA is the branded generic of Cardizem LA. ‡Dilacor XR is no longer manufactured, but included in this review because its branded generic, DILT-XR, is still on the market. §Taztia XT and Diltzac are branded generics of Tiazac. (Drugs@FDA 2019, Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations 2019) INDICATIONS Table 2. FDA-Approved Indications – Dihydropyridines ) Indication elecoxib mlodipine/ mlodipine/ Consensi Consensi Isradipine Nifedipine Felodipine C Nisoldipine Amlodipine Nicardipine Nimodipine (a Angina Pectoris Treatment of chronic stable angina * - - † - - - Data as of November 15, 2019 AG-U/KS-U/DKB Page 2 of 18 This information is considered confidential and proprietary to OptumRx. It is intended for internal use only and should be disseminated only to authorized recipients. The contents of the therapeutic class overviews on this website ("Content") are for informational purposes only. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Patients should always seek the advice of a physician or other qualified health provider with any questions regarding a medical condition. Clinicians should refer to the full prescribing information and published resources when making medical decisions. ) Indication elecoxib mlodipine/ mlodipine/ Consensi Consensi Isradipine Nifedipine Felodipine C Nisoldipine Amlodipine Nicardipine Nimodipine (a Treatment of chronic stable angina without evidence of (capsule vasospasm in patients who remain symptomatic despite , ER tablet - - - - - - adequate doses of beta blockers and/or organic nitrates or [Procardia who cannot tolerate those agents XL]) Treatment of vasospastic angina (capsule , ER tablet ‡ - - - - - [Procardia XL])§ CAD Reduce the risk of hospitalization due to angina and to reduce the risk of a coronary revascularization procedure in patients - - - - - - with recently documented CAD by angiography and without heart failure or an ejection fraction < 40% Hypertension (ER Treatment of hypertension ║ ¶ - ║ ║ tablet)║ ║ Treatment of hypertension to lower blood pressure which (ER tablet reduces the risk of fatal
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